Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
The Binding Site Inc., Rochester, Minnesota, USA.
JCI Insight. 2018 Feb 22;3(4). doi: 10.1172/jci.insight.97919.
Neurodegeneration is a central aspect of the early stages of diabetic retinopathy, the primary ocular complication associated with diabetes. While progress has been made to improve the vascular perturbations associated with diabetic retinopathy, there are still no treatment options to counteract the neuroretinal degeneration associated with diabetes. Our previous work suggested that the molecular chaperones α-crystallins could be involved in the pathophysiology of diabetic retinopathy; however, the role and regulation of α-crystallins remained unknown. In the present study, we demonstrated the neuroprotective role of αA-crystallin during diabetes and its regulation by its phosphorylation on residue 148. We further characterized the dual role of αA-crystallin in neurons and glia, its essential role for neuronal survival, and its direct dependence on phosphorylation on this residue. These findings support further evaluation of αA-crystallin as a treatment option to promote neuron survival in diabetic retinopathy and neurodegenerative diseases in general.
神经退行性变是糖尿病性视网膜病变早期的一个核心方面，糖尿病性视网膜病变是与糖尿病相关的主要眼部并发症。虽然在改善与糖尿病性视网膜病变相关的血管紊乱方面已经取得了进展，但仍然没有治疗选择来对抗与糖尿病相关的神经视网膜变性。我们之前的工作表明，分子伴侣α-晶体蛋白可能参与糖尿病性视网膜病变的病理生理学；然而，α-晶体蛋白的作用和调节仍然未知。在本研究中，我们证明了αA-晶体蛋白在糖尿病中的神经保护作用及其在残基 148 上磷酸化的调节作用。我们进一步描述了αA-晶体蛋白在神经元和神经胶质中的双重作用、其对神经元存活的必需作用以及其对该残基磷酸化的直接依赖性。这些发现支持进一步评估αA-晶体蛋白作为一种治疗选择，以促进糖尿病性视网膜病变和一般神经退行性疾病中神经元的存活。
